The present invention relates to methods for surface modification. More particularly, the present invention relates to methods for surface modification of medical materials, such as, for example, biomaterials.
For devices used in many fields, it is desirable to use materials having particular surface properties suitable for a given purpose so that the device optimally functions without causing adverse effects. One such field where it is desirable to have specific properties for the surface material of the devices is the medical field, where the surface characteristics of biomaterials are particularly important.
Biomaterials are typically made of inert metals, polymers, or ceramics to ensure durability. Furthermore, biomaterials are often desirably constructed of materials that do not adversely react with the physiological environment with which they come into contact, such as with blood or tissues. More particularly, many biomedical devices may or may not require blood compatible, infection resistant, and/or tissue compatible surfaces. For example, it is often desirable to manufacture medical devices, such as catheters, that have properties that discourage adherence of blood or tissue elements to the device. Conversely, it is also desirable for certain biomaterials, such as those for implants, to be anchored stably into the tissue environment into which they are implanted. For example, it may be desirable for specific implants, such as certain types of catheters and stents, to be non-inflammatory and anchored to the surrounding tissues. Moreover, it may be desirable for certain biomaterials to prevent bacterial growth during a course of a procedure, or as a permanent implant so as to prevent infection of a patient in contact with the biomaterial. For example, disposable surgical tools may become infected with bacteria during a course of a long operation and reuse of the tool during the operation may promote bacterial infection in the patient. For certain tools used in particular applications, it may be desirable therefore to prevent any bacterial growth on the surfaces of these tools during the course of an operation. Additionally for permanently implanted materials it would be desirable to prevent bacterial growth that would lead to a biomaterial or device centered infection. In the latter the only remedy is eventual removal of the implant. Thus, depending on the ultimate use of a biomedical device, it is often desirable to have the material surface property of a device vary according to a specific use.
To cause further advances in the biomedical field, the use of various materials should widen and their performance heightened by varying the surface properties of the material without changing its mechanical, optical, or other properties. For example, one type of biomaterial, polyolefin, can result in devices that have non-polar properties and therefore may result in poor adhesion, printability, and adaptability of its surface for coatings. Various kinds of surface treatments have been used to solve these promblems, such as corona discharge treatment, oxidation, flame treatment, surface grafting, irradiation, and direct plasma treatment. These methods have proven to have limited success due to their general ineffectiveness and expense.
Conventional techniques for coating a biomedical device with a desired surface layer typically are expensive, time-consuming, inconsistent in results, and do not ensure either a uniform layer of a surface material on the medical device or that the coating does not wear off in time. Thus, the properties of the surface layer of the device may vary between areas and thereby affect the overall surface property of the device. Furthermore, different devices subject to the same coating technique may result in different properties. Hence, there exists a need for a process that results in consistently reproducible and uniformly controllable surface conditions.
Another disadvantage of typical processes for applying a coating to a biomedical device is that each material requires a different technique to modify its surface. For example, metals, ceramics, and polymers have different surface properties and do not lend themselves to a common coating process. Polymers typically are hydrophobic or, at best, have relatively poor wetting, and therefore are difficult to coat from solutions. Furthermore, the majority of polymers used for medical devices also are relatively inert and do not possess functional groups that readily enter into direct chemical coupling reactions that could modify their surfaces. In order to overcome these limitations in polymers, surface treatments such as corona, plasma, irradiation, and chemical oxidation are used to make the surfaces more wet, or to add a functional group such as carboxyl (xe2x80x94COOH) or hydroxyl (xe2x80x94OH) to the surface.
Another important functional or reactive group that can be introduced to the surface is a free radical. This group can react with vinyl functional monomers to initiate chain reaction polymerization that results in a grafted surface. In yet another example, a polymer can be exposed to plasma treatment to generate surface free radicals. These free radicals however are short lived and lacking in surface density. Attempts to effect a chain reaction polymerization on such surfaces (graft) with monomers such as acrylamide only works on a few materials and poorly on those few materials. For example, a polyolefin material such as polypropylene may be exposed to air plasma activation, and then exposed to an acrylic monomer solution with catalysts. The results are a slight and patchy grafting with significant areas of no grafting. The reasons for these poor results have been explained by sighting two mechanisms. First, the plasma itself is a highly reactive state and so many radicals are produced that they end up reacting with each other, resulting in termination and/or neutralization of free radicals. A second mechanism is the reaction of the surface with oxygen from the air. This reaction leads to several additional degradative reactions that attack vinyl groups formed at the surface that also can be used for effective grafting.
With respect to plasma reactions, there are typically two types. First, there is plasma activation or plasma treatment with a gas that does not result in a deposition of new material to the surface. This reaction can do a number of things to the surface, including creation of new functional groups, ablation and/or cleaning of contaminants, and cross-linking. The second plasma reaction is called plasma polymerization or deposition. This is accomplished by the introduction of a reactive gas that can polymerize and/or react directly to the surface of the material. In the reaction of plasma polymerization or deposition, the resultant surface that is obtained on the material treated is dependent on the reactive gas used. For example, a polyethylene catheter may be treated with tetrafluoroethylene (TFE) gas resulting in a new surface with a polytetrafluoroethylene composition. This latter process is most often referred to as a xe2x80x9cplasma polymerizedxe2x80x9d surface. The surface is most often a thin and conformal layer and is highly cross-linked. The surface differs considerably from a surface that has a layer generated by free radical initiated grafting. Free radical grafting takes place in the absence of the glow discharge of the plasma reactor and results in a non-cross linked layer. This property is advantageous when it comes to coupling additional molecules and especially biological molecules. The reason for this is that the grafted surface allows a more three dimensional network for these coupling reactions to take place as opposed to the highly ordered and rather two dimensional nature of plasma polymerized layers. This effectively results in the ability to have a higher loading of the coupled molecules to the surface as well as a greater degree of mobility and conformational integrity of the coupled molecules that helps maintain their natural bioactivity. Biomolecules require a mobile three-dimensional environment to react, and simple adsorption based on charge attraction results in a multipoint spread out attachment that compromises the conformational integrity of the molecule. The most practical application of this principle is in affinity chromatography.
Simple plasma activation of polymeric surfaces in order to subsequently generate a free radical initiated chain polymerized graft has several problems. The primary limitation is that the most common biomaterials such as PTFE (polytetrafluoroethylene), silicone, PVC (polyvinylchloride), metals, and ceramics do not effectively generate free radicals on their surfaces. With the remaining polymers such as urethanes, acrylates, polyolefins, and others, the plasma activation results in very different surfaces with respect to reactivity. An additional disadvantage to commercial polymers is the additives present contaminate the surfaces and make direct coupling to the native polymer unstable and unpredictable. Finally, free radicals generated on a polymeric surface by plasma treatment are short lived, and this makes it very difficult to attain optimal free radical grafted surfaces.
Plasma polymerized films can uniformly cover the surface of a polymer with a new composition, but these surfaces as mentioned previously are highly ordered, and attempts to further directly couple molecules at high loadings are difficult. Attempts to plasma activate a plasma polymerized film and subsequently free radical graft to this surface remove some of the disadvantages, but still suffer from the problems of short lived free radicals, and difficulty in adjusting plasma conditions to obtain optimal graft densities.
Thus, there exists a need for a relatively quick, economical, and universal method of treating a variety of types of surface materials to result in a stable coating having desirable biocompatible properties.
This invention is directed to methods of treating the surface of materials used for devices in any field, and to the related devices treated by such methods. Preferably, the method relates to the treatment of the surface of biomaterials, such as, for example, those used in medical devices. The treatment methods as disclosed in this invention are both suitable for medical devices that are used for an extended period of time, such as, for example, stents and other like conduits and devices, and also suitable for medical devices that are used for shorter periods, such as, for example, catheters.
Accordingly, the present invention is directed to methods that substantially obviate one or more of the problems due to limitations and disadvantages of the related art. To achieve these and other advantages and in accordance with the purposes of the invention, as embodied and broadly described, an aspect of the invention is drawn to a method of modifying a surface of a device. The method includes the steps of providing the device, exposing the device to a reactive gas and plasma energy to create a plasma deposited surface on the device, and quenching the device with the reactive gas.
The method may include the step of placing the device in a plasma chamber, and infusing air into the plasma chamber, wherein the placing and infusing steps occur prior to exposing the device to plasma energy.
In another embodiment of the invention, the invention is drawn to a method of modifying a surface of device. The method includes providing the device, placing the device in a plasma chamber, infusing air into the plasma chamber, exposing the device to air and plasma energy to clean the surface, exposing the device to a reactive gas and plasma energy to create a plasma deposited surface on the device, quenching the device with the reactive gas by infusing the plasma chamber with the reactive gas, removing the device from the plasma chamber and exposing the device to a surface grafting solution for preferably a relatively short period of time, such as less than one hour, to achieve a covalently bonded surface graft. A surface reactant species, such as a biomolecule, may then be coupled to the grafted surface.
In yet another aspect, the invention is drawn to a device used for medical procedures. The medical device has a surface modified by a surface treatment process. The process includes the steps of providing the device, exposing the device to a reactive gas and plasma energy to create a plasma deposited surface on the device, and quenching the device with the reactive gas.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the methods and devices particularly pointed out in the written description and claims hereof as well as the appended drawings. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.